RESUMO
We have investigated the binding properties of [(3)H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain sections. Saturation isotherms gave K:(D) values of 27 +/- 4 and 81 +/- 22 nM: for mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited the binding to mGlu1a and mGlu5a receptors concentration-dependently. (S:)-4-Carboxyphenylglycine, (S:)-4-carboxy-3-hydroxyphenylglycine, and (R,S)-1-aminoindan-1,5-dicarboxylic acid, which completely inhibited [(3)H]quisqualate binding to the mGlu5a receptor, were inactive in a functional assay using this receptor. The distribution and abundance of binding sites in rat and human brain sections were studied by quantitative receptor radioautography and image analysis. Using 10 nM: [(3)H]quisqualate, a high density of binding was detected in various brain regions with the following rank order of increasing levels: medulla, thalamus, olfactory bulb, cerebral cortex, spinal cord dorsal horn, olfactory tubercle, dentate gyrus molecular layer, CA1-3 oriens layer of hippocampus, striatum, and cerebellar molecular layer. The ionotropic component of this binding could be inhibited by 30 microM: kainate, revealing the distribution of mGlu1+5 receptors. The latter were almost completely inhibited by the group I agonist (S:)-3,5-dihydroxyphenylglycine. The binding profile correlated well with the cellular sites of synthesis and regional expression of the respective group I receptor proteins revealed by in situ hybridization histochemistry and immunohistochemistry, respectively.
Assuntos
Encéfalo/metabolismo , Glicina/análogos & derivados , Ácido Quisquálico/farmacocinética , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Ligação Competitiva/efeitos dos fármacos , Cálcio/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glicina/farmacologia , Humanos , Imidazóis/farmacologia , Indanos/farmacologia , Líquido Intracelular/metabolismo , Ácido Caínico/farmacologia , Masculino , Especificidade de Órgãos , Quinazolinas/farmacologia , Ratos , Ratos Endogâmicos , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Medula Espinal/metabolismo , TransfecçãoRESUMO
1-O-Alkyl-2,3-diacyl-sn-glycerols, the major constituents of ratfish (Chimaera monstrosa) liver oil, serve as starting material for the preparation of 1-O-alkyl-sn-glycero-3-phosphocholines, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines, 1-O-alkyl-2-O-methyl-sn-glycero-3-phosphocholines, and 1-O-alkyl-2-O-methyl-sn-glycero-3-beta-D-glucopyranosides. Catalytic tritiation of the unsaturated alkyl moieties in these biologically active ether lipids affords the corresponding 3H-labeled substances.